DNA polymerase beta (Pol-beta) functions in base excision repair and meiosis. The high error rate of Pol-beta suggests that this polymerase might contribute to mutations, resulting in human disease. This application proposes to establish a tissue-specific knockout mouse to study the role of Pol-beta in meiosis. This research will use the Cre/loxP recombination system to direct testes-specific deletion of pol-beta. The function of Pol-beta in meiosis will be defined by histological and immunohistological examination of Pol-beta deletion mutants. In addition, a lambda phage-based mouse mutagenesis assay will be used to determine the impact of pol-beta inactivation on mutational frequency during meiosis. Finally, the yeast two-hybrid system will be used to identify proteins that interact with Pol-beta in meiosis. The proposed research will contribute to our understanding of the function of Pol-beta in vivo, as well as broaden our knowledge of meiosis.